Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neurostimulators

ABSTRACT

Test procedures for determining a neural stimulation threshold of a patient. In one embodiment, the procedure includes applying a test stimulation signal to the patient and monitoring the patient for a response to the test stimulation signal. The procedure can further include determining a first neural stimulation threshold and calculating a second neural stimulation threshold. The first neural stimulation threshold corresponds to the lowest intensity test stimulation signal that evokes a patient response. The second neural stimulation threshold corresponds to a treatment stimulation signal directed toward affecting a neural activity within the patient.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation of U.S. application Ser. No.10/350,947, filed Jan. 24, 2003, which is a Continuation-in-Part of U.S.application Ser. No. 09/978,134, filed Oct. 15, 2001, which is aContinuation-in-Part of U.S. application Ser. No. 09/802,808, filed Mar.8, 2001, which claims priority to U.S. Provisional Application No.60/217,981, filed Jul. 13, 2000, all of which are incorporated herein byreference in their entireties.

TECHNICAL FIELD

The present disclosure is related to systems and methods for reducingthe likelihood of inducing collateral neural activity while determiningthreshold parameters for electrically stimulating a region in the cortexor other area of the brain.

BACKGROUND

A wide variety of mental and physical processes are controlled orinfluenced by neural activity in particular regions of the brain. Theneural-functions in some areas of the brain (i.e., the sensory or motorcortices) are organized according to physical or cognitive functions.There are also several other areas of the brain that appear to havedistinct functions in most individuals. In the majority of people, forexample, the areas of the occipital lobes relate to vision, the regionsof the left interior frontal lobes relate to language, and the regionsof the cerebral cortex appear to be consistently involved with consciousawareness, memory, and intellect.

Many problems or abnormalities with body functions can be caused bydamage, disease and/or disorders in the brain. Effectively treating suchabnormalities may be very difficult. For example, a stroke is a verycommon condition that damages the brain. Strokes are generally caused byemboli (e.g., obstruction of a vessel), hemorrhages (e.g., rupture of avessel), or thrombi (e.g., clotting) in the vascular system of aspecific region of the brain, which in turn generally cause a loss orimpairment of a neural function (e.g., neural functions related tofacial muscles, limbs, speech, etc.). Stroke patients are typicallytreated using various forms of physical therapy to rehabilitate the lossof function of a limb or another affected body part. Stroke patients mayalso be treated using physical therapy plus an adjunctive therapy suchas amphetamine treatment. For most patients, however, such treatmentsare minimally effective and little can be done to improve the functionof an affected body part beyond the recovery that occurs naturallywithout intervention.

Neural activity is governed by electrical impulses or “actionpotentials” generated in and propagated by neurons. While in a quiescentstate, a neuron is negatively polarized and exhibits a resting membranepotential that is typically between −70 and −60 mV. Through chemicalconnections known as synapses, any given neuron receives from otherneurons excitatory and inhibitory input signals or stimuli. A neuronintegrates the excitatory and inhibitory input signals it receives, andgenerates or fires a series of action potentials when the integrationexceeds a threshold potential. A neural firing threshold may be, forexample, approximately −55 mV. Action potentials propagate to theneuron's synapses, where they are conveyed to other neurons to which theneuron is synaptically connected.

The neural activity in the brain can be accordingly influenced byelectrical energy that is supplied from a man-made source such as awaveform generator. Various neural functions can thus be promoted ordisrupted by applying an electrical current to the cortex or otherregion of the brain. As a result, researchers have attempted to treatdamage, disease and disorders in the brain using electrical or magneticstimulation signals to control or affect brain functions. One treatmentapproach, transcranial electrical stimulation (TES), involves placing anelectrode on the exterior of the scalp and delivering an electricalcurrent to the brain through the scalp and skull. Another treatmentapproach, transcranial magnetic stimulation (TMS), involves producing ahigh-powered magnetic field adjacent to the exterior of the scalp overan area of the cortex. Yet another treatment approach involves directelectrical stimulation of neural tissue using implanted electrodes.

A neural stimulation signal may comprise a series or train of electricalor magnetic pulses that can affect neurons within a target neuralpopulation, and may be defined or described in accordance withstimulation signal parameters including pulse amplitude, pulsefrequency, duty cycle, stimulation signal duration, and/or otherparameters. Electrical or magnetic stimulation signals applied to apopulation of neurons can depolarize neurons within the populationtoward their threshold potentials. Depending upon stimulation signalparameters, this depolarization can cause neurons to generate or fireaction potentials. Neural stimulation that elicits or induces actionpotentials in a functionally significant proportion of the neuralpopulation to which the stimulation is applied is referred to assupra-threshold stimulation; neural stimulation that fails to elicitaction potentials in a functionally significant proportion of the neuralpopulation is defined as sub-threshold stimulation. In general,supra-threshold stimulation of a neural population triggers or activatesone or more functions associated with the neural population, butsub-threshold stimulation by itself fails to trigger or activate suchfunctions. Supra-threshold neural stimulation can induce various typesof measurable or monitorable responses in a patient. For example,supra-threshold stimulation applied to a patient's motor cortex caninduce muscle fiber contractions.

Although electrical or magnetic stimulation of neural tissue may bedirected toward producing an intended type of therapeutic,rehabilitative, or restorative neural activity, such stimulation mayresult in collateral neural activity. In particular, neural stimulationdelivered beyond a certain intensity, level, or amplitude can give riseto seizure activity and/or other types of collateral activity, which maybe undesirable and/or inconvenient in a neural stimulation situation.

Seizure activity may originate at a seizure focus, which is a collectionof neurons (e.g., on the order of 1000 neurons) exhibiting acharacteristic type of synchronous firing activity. In particular, eachneuron within a seizure focus exhibits a firing response known as aparoxysmal depolarizing shift (PDS). The PDS is a large magnitude, longduration depolarization that triggers a neuron to fire a train or burstof action potentials. Properly functioning feedback and/or feed-forwardinhibitory signaling mechanisms cause an ensuing afterhyperpolarization,through which the neuron's membrane potential returns to ahyperpolarized state below its firing threshold. Following theafterhyperpolarization, the neuron may undergo another PDS.

The afterhyperpolarization limits the duration of the PDS, therebyhelping to ensure that synchronous neural firing activity remainslocalized to the seizure focus. Inhibitory feedback signaling providedby neurons surrounding a seizure focus, commonly referred to as surroundinhibition, is particularly important in constraining seizure activityto the seizure focus. In the event that inhibitory signaling mechanismsfail and/or are unable to overcome or counter PDS activity, neuronswithin the seizure focus recruit other neurons to which they aresynaptically coupled into their synchronous firing pattern. As a result,synchronous firing activity spreads beyond the seizure focus to otherareas of the brain. This can lead to a cascade effect in which seizureactivity becomes increasingly widespread and accompanying clinicalmanifestations become increasingly significant.

In view of the foregoing, it may be very important in any given neuralstimulation situation to determine an appropriate stimulation signalamplitude, level, or intensity. However, an appropriate stimulationsignal level may vary on a per-patient basis and possibly over time forany particular patient. Notwithstanding, determination of a neuralstimulation threshold corresponding to a minimum or near-minimumstimulation signal level that induces or generates a measurable ormonitorable patient response can provide a reference point forestablishing a stimulation signal intensity appropriate for a neuralstimulation session.

Various types of neural stimulation thresholds exist. For example, anelectromyography or electromyographic (EMG) threshold may be defined asa lowest or near-lowest level of neural stimulation that generates anEMG signal of a particular magnitude. An EMG signal provides ameasurement of electrical discharges associated with the innervation ofmuscle fibers by one or more motor neurons, and the onset of musclefiber contraction in response to such electrical discharges. As anotherexample, a sensation threshold may be defined as a lowest or near-lowestlevel of neural stimulation at which a patient notices, perceives, orexperiences a physical sensation such as a tingling or vibration in amuscle group or limb. As yet another example, a movement threshold maybe defined as a lowest or near-lowest level of neural stimulation thatinduces a noticeable movement in a patient's limb.

Unfortunately, neural stimulation threshold testing can itself inducecollateral neural activity. During a typical neural stimulationthreshold test procedure, a very low amplitude test stimulation signalis initially applied to a patient. The amplitude of the test stimulationsignal is then increased incrementally, while other test stimulationsignal parameters (e.g., frequency, pulse characteristics, duty cycle,etc . . .) remain unchanged or unmodified. As its amplitude isincreased, the test stimulation signal is delivered to the patient in anuninterrupted or continuous manner. A lowest or near-lowest teststimulation signal amplitude that evokes a given type of patientresponse is correspondingly defined as the neural stimulation threshold.The patient is subsequently treated using a stimulation signal havingparameters identical to those of the test stimulation signal, with thepossible exception of stimulation signal amplitude, which may be apredetermined value based on the neural stimulation threshold.

Stimulation signal characteristics and manners in which stimulationsignals are applied to a target neural population can significantlyaffect the likelihood of inducing collateral neural activity.Conventional neural stimulation threshold test procedures fail toadequately address this consideration, and thus may be susceptible toinducing seizure activity and/or other types of collateral neuralactivity. Hence, there is a need for systems and methods that reduce thelikelihood of inducing such activity during neural stimulation thresholdtesting.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a system for neural stimulationthreshold testing according to an embodiment of the invention.

FIG. 2 is a graph illustrating several parameters that may describe orcharacterize a stimulation signal.

FIG. 3 is a flowchart illustrating various methods for neuralstimulation threshold testing according to an embodiment of theinvention.

FIG. 4 is a flowchart illustrating various methods for neuralstimulation threshold testing according to another embodiment of theinvention.

DETAILED DESCRIPTION

The following disclosure describes systems and methods for reducing thelikelihood of inducing collateral neural activity during the applicationof test stimulation signals to a patient for the purpose of determininga threshold stimulation level that induces or evokes a particular typeof patient response, behavior, activity, sensation, perception, and/orreaction. In the context of the present invention, collateral neuralactivity may comprise seizure activity and/or essentially any other typeof neural activity that may be undesirable, unwanted, unintended, and/orcounterproductive relative to an intended or desired neural activityassociated with neural stimulation threshold testing.

Various methods in accordance with the present invention are directedtoward neural stimulation threshold test procedures that temporallymanage the application of test stimulation signals to a patient. Neuralstimulation lasting beyond several seconds (e.g., approximately 5seconds) can lead to prolonged neural firing responses known asafterdischarges. Afterdischarges in a target neural population increaseor tend to increase neural activity in the population, which may exciteother neurons synaptically coupled to the target population.Afterdischarges can therefore increase the likelihood of inducingcollateral neural activity. Neural stimulation threshold test proceduresin accordance with the present invention may therefore apply limitedduration test stimulation signals to patients.

Neural stimulation applied to a target neural population can affect thefuture excitability or firing likelihood of neurons in the targetpopulation. In particular, recently stimulated neurons may exhibitenhanced excitability in the presence of subsequent stimulation. Aneural population that receives sub-threshold stimulation during a firsttime period may exhibit an increased firing susceptibility in thepresence of same stimulation applied during a second time period whenthe second time period and the first time period are separated by only abrief interval (e.g., seconds or several seconds). Moreover, neuralactivity, such as afterdischarges, may persist for many milliseconds orseconds after a stimulation signal is interrupted or terminated. Hence,neural stimulation threshold test procedures in accordance with thepresent invention may additionally or alternatively provide for aquiescent time interval between successive threshold determinationattempts during which test stimulation signals are not applied ordelivered to the target neural population.

Various methods in accordance with the present invention mayadditionally or alternatively be directed toward neural stimulationthreshold test procedures in which test stimulation signals and atreatment stimulation signal used to treat a patient may parametricallydiffer beyond their amplitudes. For example, depending upon stimulationsignal parameters, neurons within a target population may respond to astimulation signal in a synchronous manner. In particular, the abilityof neurons to synchronously respond to or follow a stimulation signal isa function of the stimulation signal's frequency. Neurons can readilyfollow a stimulation signal up to a frequency of approximately 100Hertz, but beyond this frequency their ability to follow the stimulationsignal degrades. Supra-threshold stimulation delivered to a targetneural population at a frequency that—neurons can readily follow maydrive synchronous firing activity within the population. In view of theforegoing, a neural stimulation threshold test procedure in accordancewith the present invention may measure a first neural stimulationthreshold using one or more test stimulation signals having a firstfrequency; and subsequently calculate a second neural stimulationthreshold corresponding to a treatment stimulation signal that may havea second frequency different from the first frequency. The calculationof the second neural stimulation threshold may be performed inaccordance with one or more transformation equations, as described indetail below.

FIG. 1 is a schematic illustration of a system 100 for neuralstimulation threshold testing according to an embodiment of theinvention. In one embodiment, the system 100 comprises a stimulus unit120 configured to deliver stimulation signals to a patient 190 through apatient interface 109. The system 100 may further include a sensing unit180 coupled to the patient 190 and the stimulus unit 120.

The stimulus unit 120 is capable of generating and outputtingstimulation signals, which comprise electrical and/or magnetic signalsor stimuli. The stimulus unit 120 may perform, direct, and/or facilitateneural stimulation threshold test procedures in a manner that reducesthe likelihood of inducing collateral neural activity in accordance withthe present invention. Neural stimulation threshold test procedures mayinvolve the application of one or more test stimulation signals to apatient 190 in manners described in detail below. The stimulus unit 120may additionally perform, direct, and/or facilitate neural stimulationtreatment procedures to treat a particular neurological condition and/oraffect or influence a given type of neural activity. Neural stimulationtreatment procedures involve the application of a treatment stimulationsignal to a patient. The treatment stimulation signal, for example, istypically at a level or amplitude that corresponds to a result obtainedduring neural stimulation threshold test procedures (e.g., 20% to 80% ofa neural stimulation threshold).

The stimulus unit 120 may comprise a controller 130, a pulse system 140,and a set of controls/indicators 150. The controller 130 may include aprocessor, a memory, and a programmable computer medium. The controller130 may be implemented as a computer or microcontroller, where theprogrammable medium comprises software loaded into the memory, and/orhardware that performs, directs, and/or facilitates neural stimulationthreshold test procedures in accordance with the methods of the presentinvention. The controls/indicators 150 can include a display device, aninput/output device, and/or other types of devices for exchangingcommands and/or output with a computer.

The pulse system 140 can generate energy pulses, and send such pulses tothe patient interface 109. In one embodiment, the pulse system 140 formsa portion of a Transcranial Magnetic Stimulation (TMS) device throughwhich externally applied magnetic stimulation signals create electricalcurrents in the patient's brain. In such an embodiment, the patientinterface 109 may comprise an electromagnetic coil arrangement in amanner understood by those skilled in the art. In another embodiment,the pulse system 140 forms a portion of an electrical stimulationdevice; in this case the patient interface 109 may comprise an electrodearray configured to deliver electrical stimulation signals to thepatient 190 as described in detail hereafter.

The patient interface 109 shown in FIG. 1 comprises an electrode array110 including a support member 112 and a plurality of electrodes 114carried by the support member 112. The electrode array 110 is generallyimplanted into the patient 190 and configured for cortical stimulation,deep brain stimulation, and/or other types of neural stimulation. Theelectrode array 110 may comprise a cortical neural-stimulation device,such as a device described in U.S. application Ser. No. 09/802,808,incorporated herein by reference. The electrodes 114 may be coupled tothe stimulus unit 120 by a link 116, which may be wire-based orwireless.

The electrode array 110 and the pulse system 140 can be integrated intoa single implantable stimulation apparatus, as described in U.S.application Ser. No. 09/082,808. An integrated pulse system 140 andelectrode array 110 may be configured for implantation into a patient'sskull such that the electrodes 114 can contact the patient's dura matteror pia matter in a given cortical region. Such a device can have aninternal power source that can be implanted into the patient 190, and/oran external power source coupled to the pulse system 140 viaelectromagnetic coupling or a direct connection. In alternateembodiments, the pulse system 140 is an external unit that is notimplanted into the patient 190. An external pulse system 140 can providestimuli to the electrodes 114 using RF energy, electromagnetism, or wireterminals exposed on the patient's scalp.

The sensing unit 180 may comprise a system or apparatus for measuring ormonitoring one or more types of patient reactions evoked or induced inresponse to test stimulation signals applied during neural stimulationthreshold test procedures. The sensing unit 180 can be coupled to thestimulus unit 120 by at least one link 186, which may be wire-basedand/or wireless. The stimulus unit 120 may issue a signal over the link186′ to synchronize the application of test stimulation signals to thepatient 190 with sensing unit measuring, monitoring, and/or recordingoperations. Depending upon embodiment details, the sensing unit 180 mayalso use the link 186 to communicate status information and/ormeasurement results to the stimulus unit 120.

In one embodiment, the sensing unit 180 comprises an EMG device coupledto a plurality of electrodes or leads 182. The EMG device may detect ormonitor motor evoked potentials (MEPs) associated with muscle fiberinnervation in a manner understood by those skilled in the art. An EMGthreshold may be defined, for example, as a lowest or near-lowest levelof neural stimulation that induces an MEP that departs from baselineelectrical activity by an amplitude greater than 50 microvoltspeak-to-peak under 1000× amplification and 20-1000 Hertz bandpassconditions. The electrodes 182 may comprise surface, percutaneous,and/or implanted probes, which may be positioned or configured tomeasure electrical activity associated with one or more muscles ormuscle groups. In one embodiment, the electrodes 182 include a groundlead and bipolar surface leads configured to monitor MEPs in aninterosseus muscle, a wrist extensor, a wrist flexor, and/or othermuscles.

Various embodiments of the present invention may alternatively oradditionally detect or determine other types neural stimulationthresholds, such as a sensation threshold, a movement threshold, anElectroencephalogram (EEG) threshold, a Magnetoencephalogram (MEG)threshold, and/or an imaging threshold. The structure and/or function ofthe sensing unit 180 may correspond to the type of neural stimulationthreshold under consideration. For example, to facilitate detection of amovement threshold, the sensing unit 180 may comprise a set of motiondetectors, accelerometers, and/or strain gauges configured to detect ormonitor one or more types of patient movements. To detect or determinean EEG threshold, the sensing unit 180 may comprise an EEG systemconfigured to monitor changes in a patient's EEG during neuralstimulation threshold test procedures. Such an EEG system may includeand/or utilize electrodes positioned upon the patient's scalp, and/orintracranially upon a brain surface or in a subcortical region.

To detect or determine an MEG threshold, the sensing unit 180 maycomprise an MEG system configured to monitor variations in the patient'sMEG in response to test stimulation signals. To measure or determine animaging threshold, the sensing unit 180 may comprise a neural imagingsystem configured to monitor and image a patient's neural activityduring neural stimulation threshold test procedures. Suitable neuralimaging systems include Magnetic Resonance Imaging (MRI) systems,functional MRI (fMRI) systems, or Positron Emission Tomography (PET)systems.

Different types of neural stimulation thresholds may vary with respectto measurement or observation subjectivity, and/or sensitivity tostimulation signal intensity. In general, determination of an EMGthreshold may be a less subjective process than determination of amovement threshold, which may be a less subjective process thandetermination of a sensation threshold. Also, an EMG threshold may betriggered or induced at a lower stimulation signal intensity than asensation or a movement threshold. In general, a sensation threshold maybe triggered or induced at a lower stimulation signal intensity than amovement threshold, although this need not always be the case.Determination of movement and/or sensation thresholds may involve orrely upon human perception and verbal and/or visual feedback, and maynot require the use of a sensing unit 180.

As previously indicated, the stimulus unit 120 is configured to deliverstimulation signals to a patient 190; the stimulation signals maycomprise test stimulation signals and/or treatment stimulation signals.FIG. 2 is a graph illustrating several parameters that may define,describe, or characterize stimulation signals. A stimulus start timet_(o) defines an initial point at which a stimulation signal is appliedto the patient interface 110. In one embodiment, the stimulation signalmay be a biphasic waveform comprising a series of biphasic pulses, andwhich may be defined, characterized, or described by parametersincluding a pulse width t₁ for a first pulse phase; a pulse width t₂ fora second pulse phase; and a pulse width t₃ for a single biphasic pulse.The parameters can also include a stimulus repetition rate 1/t₄corresponding to a pulse repetition frequency; a stimulus pulse dutycycle equal to t₃ divided by t₄; a stimulus burst time t₅ that defines anumber of pulses in a pulse train; and/or a pulse train repetition rate1/t₆ that defines a stimulus burst frequency. Other parameters include apeak current intensity 11 for the first pulse phase and a peak currentintensity I₂ for the second pulse phase. Those skilled in the art willunderstand that pulse intensity or amplitude may decay during one orboth pulse phases, and a pulse may be a charge-balanced waveform. Thoseskilled in the art will further understand that in an alternateembodiment, pulses can be monophasic or polyphasic.

FIG. 3 is a flowchart illustrating various methods for neuralstimulation threshold testing according to an embodiment of theinvention. In one embodiment, a method 300 may include a parameterdetermination procedure 302 involving determination, selection, orspecification of test stimulation signal parameters that may reduce alikelihood of inducing collateral neural activity. Depending uponembodiment details, one or more types of test stimulation signalparameter sets, selections, and/or settings may be preprogrammed intothe stimulus unit 120. A stimulus unit operator (e.g., a medicalprofessional) may select a particular set of test stimulation signalparameters using the stimulus unit's controls/indicators 150. Exemplarytest stimulation signal parameter selections that may reduce thelikelihood of inducing collateral neural activity are described indetail below with reference to FIG. 4.

The method 300 may additionally include a signal management procedure304 that involves managing the temporal application of test stimulationsignals to a patient 190 in a manner that reduces the likelihood ofinducing collateral neural activity. A stimulus unit operator may usethe stimulus unit's controls/indicators 150 to initiate the signalmanagement procedure 304. Particular manners of temporally managing teststimulation signal application in accordance with the present inventionare described in detail below with reference to FIG. 4. The method 300may additionally include an observation or measurement procedure 306that involves observing and/or measuring one or more neural stimulationthresholds based upon one or more patient reactions and/or behaviorsinduced in response to the test stimulation signals. The observationprocedure 306 may be performed using the sensing unit 180 and/or humanperception and feedback.

The method 300 may further include a calculation procedure 308 involvingcalculation, mapping, and/or determination of a neural stimulationthreshold corresponding to a treatment stimulation signal that is to beapplied to the patient 190 for treating a neurological condition and/oraffecting neural activity. The treatment stimulation may beparametrically distinct from one or more test stimulation signals withrespect to one or more parameters. Operations performed and/or directedby the calculation procedure 308 may be based upon one or more measuredand/or observed neural stimulation thresholds. The calculation procedure308 may involve the use of one or more conversion or mapping functionsand/or data tables stored in a memory of the stimulation unit. Suchfunctions and/or data tables may be based upon known relationshipsand/or one or more empirical measurement histories capable ofcorrelating test stimulation signal parameters with treatmentstimulation signal parameters for a range of neural stimulationthresholds as measured or observed in association with the observationprocedure 306.

FIG. 4 is a flowchart illustrating various methods for neuralstimulation threshold testing according to another embodiment of theinvention. In one embodiment, a method 400 includes a parameterdetermination procedure 402 that involves determining, specifying,and/or selecting test stimulation signal parameters that may reduce alikelihood of inducing collateral neural activity. In one embodiment,the pulse repetition frequency within a test stimulation signal may behigher than that within a treatment stimulation signal in order toreduce or minimize the likelihood that a significant number of neuronswithin a target neural population can synchronously respond to or followthe test stimulation signal. In general, a test stimulation signal needsto activate few or relatively few neurons within a target population toinvoke or elicit a measurable and/or observable patient response. Thus,the pulse repetition frequency of a test stimulation signal may behigher than a neural frequency that produces a significant degradationin behavior or function (e.g., above approximately 100 Hertz), withoutadversely affecting the likelihood that a sufficient number of neuronscan fire and evoke a patient response. In accordance with the presentinvention, exemplary test stimulation signal pulse repetitionfrequencies may be approximately 250 Hertz to approximately 400 Hertz,and in particular at the endpoints of this range.

An average amount of electrical current, charge, or energy delivered toa target neural population increases with increasing pulse repetitionfrequency, given constant or essentially constant test stimulationsignal duration. As a result, a test stimulation signal having a higherpulse repetition frequency may be expected to elicit or evoke ameasurable and/or observable patient response at a lower current levelthan an equivalent duration test stimulation signal having a lower pulserepetition frequency.

The method 400 may further include a signal application procedure 404that involves application or initiation of application of (a) a firstlimited duration test stimulation signal having a low or very lowintensity or amplitude to a target neural population within the patient190; or (b) a next limited duration test stimulation signal having anincrementally or slightly higher intensity or amplitude than a previoustest stimulation signal to the target neural population. The use oflimited duration test stimulation signals may reduce or minimize thelikelihood of generating prolonged neural firing responses such asafterdischarges that can increase neural excitation outside of thetarget population to which the test stimulation signals are applied. Ingeneral, a limited duration test stimulation signal in accordance withthe present invention may be shorter than approximately 5 seconds.

The duration of a test stimulation signal applied in accordance with thepresent invention may depend upon a type of neural stimulation thresholdcurrently under consideration. Thus, a limited duration test stimulationsignal applied when determining one type of threshold may be shorter orlonger than a limited duration test stimulation signal applied whendetermining another type of threshold. In general, a shorter durationtest stimulation signal may deliver a lower average amount of electricalcurrent, charge, or energy to the target neural population than a longerduration test stimulation signal given equivalent or generallyequivalent pulse repetition frequencies. Hence, a shorter duration teststimulation signal may require a higher electrical current intensity,level, or amplitude to induce or evoke a given type of patient response.

With respect to determination of a movement threshold, a shorterduration test stimulation signal may evoke or induce a sharper, betterdefined, and hence more easily observable patient movement than a longerduration test stimulation signal. With respect to sensation thresholddetermination, the duration of a test stimulation signal may need to besufficient to enable a patient 190 to accurately perceive and/or confirmperception of an induced sensation. Thus, in one embodiment, the signalapplication procedure 404 may apply test stimulation signals lasting atleast approximately 1 second or less when the method 400 involvesdetermination of a movement threshold; and/or apply test stimulationsignals lasting approximately 3 seconds when the method 400 involvesdetermination of a sensation threshold.

An EMG threshold may be determined in accordance with a variety of EMGmeasurement and/or EMG signal analysis techniques. The signalapplication procedure 404 may apply test stimulation signals having aduration corresponding to an EMG measurement and/or EMG signal analysistechnique currently under consideration. In accordance with the signalapplication procedure 404, the stimulus unit 120 may issue asynchronization signal to the sensing unit 180 coincident or essentiallycoincident with the output of a test stimulation signal to initiate EMGsignal monitoring or recording operations in a manner understood bythose skilled in the art.

In one embodiment, the signal application procedure 404 may apply teststimulation signals to the patient 190 lasting approximately severalmilliseconds or on the order of tens of milliseconds when the sensingunit 180 is configured for EMG threshold measurement. An exemplary teststimulation signal duration corresponding to EMG threshold determinationmay be approximately 16 milliseconds. In such an embodiment, the signalapplication procedure 404 may repeat the application of a given teststimulation signal to the patient 190 multiple times to increase an EMGsignal to noise ratio (i.e., to average out noise); repeatedapplications of the test stimulation signal may be separated by aminimum quiescent time interval as further described below. Thedetermination of an EMG threshold using test stimulation signals havinga duration on the order of milliseconds or tens of milliseconds mayperformed in a manner analogous or generally analogous to conventionalnerve conduction studies. In another embodiment, the signal applicationprocedure 404 may apply test stimulation signals to the patient 190lasting approximately 1 second to 3 seconds.

In addition to the signal application procedure 404, the method 400 mayinclude a monitoring procedure 406 that involves monitoring or observingthe patient 190 and determining whether a patient behavior or reactionhas been evoked or induced in response to the most recently applied teststimulation signal. The monitoring procedure 406 may involve the sensingunit 180 and/or human perception and feedback. In the event that themethod 400 involves determination of an EMG threshold, the monitoringprocedure 406 may record and/or measure an EMG response during one ormore portions of a test stimulation and/or throughout its entirety. Themonitoring procedure 406 may additionally or alternatively perform EMGsignal analysis operations to enhance MEP detectability. Such EMG signalanalysis operations may include determination of changes in MEP firingor activation rates, determination of changes in MEP activation complexdurations or temporal widths, root-mean-square (RMS) amplitude analysis,power spectrum analysis, correlation analysis, and/or one or more otherstatistical analyses.

The method 400 may also include an adjustment procedure 408 involvingmodification or adjustment of test stimulation signal intensity oramplitude if no patient response was evoked in association with thesignal application procedure 404. In the absence of an evoked response,test stimulation signal intensity may be increased in accordance with aparticular increment, for example, by 0.5 or 1.0 milliamps, or by agiven percentage. The method 400 may additionally include a waitingprocedure 410 involving waiting or pausing for a minimum quiescent timeinterval following application of a most recent test stimulation signalto the patient 190. After the minimum quiescent time interval haselapsed, the method 400 may return to the signal application procedure404.

The use of a minimum quiescent time interval after the application of agiven limited duration test stimulation signal may reduce or minimizethe likelihood that neurons within the target neural population willhave an increased firing susceptibility or re-excitation likelihoodduring application of a subsequent test stimulation signal. A minimumquiescent time interval may range from several seconds to severalminutes. In an exemplary embodiment, the minimum quiescent time intervalis approximately 1 minute. In an alternate embodiment, the minimumquiescent time interval may be shortened or increased depending upon acumulative number of test stimulation signals that had been applied tothe patient 190.

The method 400 may additionally include a threshold measurementprocedure 420 involving measurement or determination of a neuralstimulation threshold corresponding to the most recently applied teststimulation signal that evoked or induced a patient reaction orresponse. In one embodiment, the neural stimulation thresholdcorresponding to a given test stimulation signal is the electricalcurrent level, intensity, or amplitude at which the test stimulationsignal evoked or induced a particular type of patient response.

The method 400 may further include a threshold calculation procedure 422involving calculation of a neural stimulation threshold corresponding toa treatment stimulation signal to be applied to the patient. Incalculating a neural stimulation threshold corresponding to a treatmentstimulation signal, the threshold calculation procedure 422 may use oneor more transformation formulas and/or conversion relationships, whichmay be programmably stored within the stimulus unit 120. Suchtransformation formulas and/or conversion relationships may be basedupon known parameter relationships and/or empirical data measured acrossa variety of test stimulation signal parameter configurations, and theymay be generated using curve fitting and/or numerical modelingprocedures. In one embodiment, a transformation formula appropriate fortest stimulation signals and treatment stimulation signals approximately3 seconds or longer in duration may be of the following general form:

I ₂(f ₂)=I ₁(f)*(1+k*(f ₁ **q))/((1+k*(f ₂ **q))   [1]

In the above equation, I₂ may be a peak, average, or RMS current levelthat defines or establishes a calculated neural stimulation thresholdcorresponding to the treatment stimulation signal; f₂ is a pulserepetition frequency associated with the treatment stimulation signal;I₁ is a measured neural stimulation threshold corresponding to a teststimulation signal; f₁ is a pulse repetition frequency corresponding tothis test stimulation signal; and k and q are constants. The values of kand q may depend upon the nature of the test stimulation signals and/orthe treatment stimulation signal. In an exemplary embodiment, for anodicmonopolar test stimulation signals, k and q may respectively equal−0.9637 and 0.0249. For bipolar test stimulation signals, k and q mayrespectively equal −1.0047 and 0.0032.

The above conversion formula may scale linearly, quasi-linearly, ornonlinearly for test stimulation signal durations shorter than 3seconds; the manner of scaling may depend upon how closely a teststimulation signal's duration approaches 3 seconds. In general, thoseskilled in the art will understand that additional and/or other types oftransformation formulas may be defined, derived, and/or determined inaccordance with particular test and/or treatment stimulation signalparameter characteristics under consideration.

A calculated neural stimulation threshold may be larger or smaller thanthe measured or observed neural stimulation threshold, depending upontest stimulation signal parameters and treatment stimulation signalparameters. The treatment signal may be parametrically distinct from thetest stimulation signals; in particular, the treatment stimulationsignal may have a different (e.g., lower) pulse repetition frequencyand/or a longer (possibly continuous) duration than the test stimulationsignals. The treatment stimulation signal may be delivered to the targetneural population at an intensity, level, or amplitude that is aparticular function or fraction of the calculated neural stimulationthreshold.

Various methods for neural stimulation threshold testing in accordancewith the present invention may employ additional, fewer, and/or otherprocedures than those described above. For example, test stimulationsignals may differ from a treatment stimulation signal with respect toadditional or other parameters than those described above. As anotherexample, a procedure may include a step of verifying a calculated neuralstimulation threshold by applying a treatment stimulation signal to thepatient 190 at the calculated threshold, and determining whether apatient reaction occurs that is equivalent or generally equivalent tothat which occurred during test stimulation signal application. Aprocedure may also record and store event information, data, and/ormeasurements obtained during test stimulation signal application. Thedisclosure herein provides for these and other variations, and islimited only by the following claims.

1. A neuro-stimulation system, comprising: an electrode array having animplantable support member configured to be implanted into a patient anda plurality of therapy electrodes carried by the support member; a pulsesystem operatively coupled to the therapy electrodes, the pulse systemdelivering a stimulus to the therapy electrodes; and a controlleroperatively coupled to the pulse system, the controller including acomputer operable medium containing instructions that generate commandsignals that define the stimulus delivered by the pulse system anddetermine a desired configuration for the therapy electrodes and/or adesired stimulus to be delivered to the therapy electrodes based uponfeedback input to the controller.
 2. The system of claim 1 wherein thetherapy electrodes are independently coupled to the pulse system suchthat the pulse system can activate and/or deactivate individual therapyelectrodes.
 3. The system of claim 1 wherein the pulse system and theelectrode array are components of an integrated unit configured to beimplanted in the patient at a stimulation site.
 4. The system of claim 1wherein the electrode array is configured to be implanted at astimulation site in the patient and the pulse system is separate fromthe electrode array and configured to be implanted at a site in thepatient remote from the stimulation site, and the pulse system beingcoupled to the electrode array by a conductive line implanted in thepatient.
 5. The system of claim 1 wherein the controller is configuredto be external to the patient and the pulse system is configured to beimplanted in the patient, and wherein the pulse. system is linked to thecontroller via a direct link or an indirect link such that thecontroller can direct the pulse system to activate and/or deactivate theelectrodes independently.
 6. The system of claim 1, further comprising asensing device configured to be attached to a sensing location of thepatient, the sensing device generating response signals defining thefeedback input into the controller; and wherein the computer operablemedium contains instructions that evaluate the response signals from thesensing device.
 7. The system of claim 6 wherein the sensing devicecomprises a sense electrode configured to be attached to the patient ata sense location to sense a response to the stimulus applied to thetherapy electrodes.
 8. The system of claim 6 wherein the sensing devicecomprises a sense electrode configured to be attached to the patient ata sense location and an EMG unit coupled to the sense electrode.
 9. Thesystem of claim 6 wherein the sensing device comprises a functional MRIdevice that detects locations of neural-activity in the brain.
 10. Thesystem of claim 6 wherein the computer operable medium of the controllercomprises a computer readable medium containing instructions causing thecontroller to perform the following method: applying an electricalstimulus having a plurality of stimulus parameters to a selectedconfiguration of the therapy electrodes; sensing a response to theapplied electrical stimulus using the sensing device; determiningwhether the response is within a desired range or an improvement over aprevious sensed response from a different electrical stimulus and/or adifferent configuration of therapy electrodes; selecting an alternateconfiguration of the therapy electrodes and/or an alternate electricalstimulus; repeating the applying, sensing, determining and selectingprocedures using the alternate configuration of the therapy electrodesand/or the alternate electrical stimulus; and choosing a configurationof therapy electrodes and/or an electrical stimulus corresponding to asensed response that is within a desired range and/or is an improvementcompared to other sensed responses.
 11. The system of claim 6 whereinthe computer operable medium of the controller comprises a computerreadable medium containing instructions causing the controller toperform the following method: sending a command signal from thecontroller to the pulse system; delivering an electrical pulse from thepulse system to a configuration of the therapy electrodes; sensing aresponse to the electrical pulse using the sensing device; receiving aresponse signal from the sensing device at the controller; in thecontroller, determining whether the signal is within a desired range oran improvement over a previous response signal from another electricalpulse and/or another configuration of the therapy electrodes, andselecting an alternate configuration of the therapy electrodes and/or analternate electrical pulse; repeating the sending, delivering, sensing,receiving, and determining procedures using the alternate configurationof therapy electrodes and/or the alternate electrical pulse; and in thecontroller, identifying an effective pulse therapy electrodeconfiguration and/or electrical pulse; and storing the effective therapyelectrode configuration and/or electrical parameter in a memory of thecontroller.
 12. The system of claim 6 wherein the computer operablemedium of the controller comprises a computer readable medium containinginstructions causing the controller to perform the following method:installing the electrode array at a therapy site of a patient;installing the sensing device at a sense location of the patient;selecting a setup configuration of the therapy electrodes and a controlstimulus of electrical parameters; applying the control stimulus to thetherapy electrodes; sensing a response in the patient with the sensingdevice and generating a response signal; in the controller, evaluatingthe response signal by comparing the response signal with at least oneof a desired response signal and/or an antecedent response signal sensedby the sensing device that have been stored in a memory of thecontroller; in the controller, automatically choosing an alternateconfiguration of therapy electrodes according to the evaluation of theresponse signal with the desired response signal and/or the antecedentresponse signal; reapplying the control stimulus to the alternateconfiguration of therapy electrodes and sensing a response signal usingthe sensing device; and repeating the evaluating, choosing andreapplying procedures until the response signal is within a desiredrange and/or a desired number of therapy electrode configurations havebeen tested.
 13. The system of claim 6 wherein the computer operablemedium of the controller comprises a computer readable medium containinginstructions causing the controller to perform the following method:installing the electrode array at a therapy site of a patient;installing the sensing device at a sense location of the patient;applying an electrical stimulus having a plurality of stimulusparameters to a control configuration of therapy electrodes; sensing aresponse in the patient with the sensing device and generating aresponse signal; in the controller, evaluating the response signal bycomparing the response signal with at least one of a desired responsesignal and/or an antecedent response signal sensed by the sensing devicestored in a memory of the controller; in the controller, automaticallychoosing an alternate set of stimulus parameters according to theevaluation of the response signal with the desired response signaland/or the antecedent response signal; reapplying the alternate set ofstimulus parameters to the setup configuration of therapy electrodes andsensing a response signal using the sensing device; and repeating theevaluating, choosing and reapplying procedures until the response signalis within a desired range and/or a desired number of stimulus parametershave been tested.
 14. The system of claim 6 wherein the computeroperable medium of the controller comprises a computer readable mediumcontaining instructions causing the controller to perform the followingmethod: selecting an initial set of stimulation parameters for aninitial electrical stimulus; applying the initial electrical stimulus toa configuration of the therapy electrodes at a target stimulation siteof the patient; sensing a response signal at a sensing site of thepatient that corresponds to the initial electrical stimulus applied tothe therapy electrodes; independently adjusting a current intensityuntil a threshold electrical stimulus is identified, the thresholdelectrical stimulus having a threshold current intensity at which aresponse is first identified in a population of neurons of the targetsite; and applying a sub-threshold electrical stimulus to theconfiguration of therapy electrodes, the sub-threshold electricalstimulus having a current intensity less than the current intensity ofthe threshold electrical stimulus.
 15. In a computer, a method ofautomatically determining a favorable neuro-stimulation program for apatient, comprising: applying an electrical stimulus having a pluralityof stimulus parameters to a selected configuration of the therapyelectrodes that have been installed at a target therapy site of apatient; sensing a response to the applied electrical stimulus at asensing device that has been installed at a sense location of thepatient; determining whether the response is within a desired range oran improvement over a previous sensed response from a differentelectrical stimulus and/or a different configuration of therapyelectrodes; selecting an alternate configuration of therapy electrodesand/or an alternate electrical stimulus; repeating the applying,sensing, determining and selecting procedures using the alternateconfiguration of therapy electrodes and/or the alternate electricalstimulus; and choosing a configuration of therapy electrodes and/or anelectrical stimulus corresponding to a sensed response that is within adesired range and/or provides a better result compared to other sensedresponses.
 16. The method of claim 15 wherein the selecting procedurecomprises computing an alternate stimulus parameter while maintaining aconstant electrode configuration, and wherein computing the alternatestimulus parameter comprises correlating a plurality of differentstimuli applied to the constant electrode configuration withcorresponding sensed responses to determine a stimulus/response trendand estimating a new stimulus parameter that is expected to improve theefficacy according to the stimulus/response trend.
 17. The method ofclaim 15 wherein the selecting procedure comprises computing analternate electrode configuration while maintaining constant stimulusparameters, and wherein computing the alternate electrode configurationcomprises correlating a plurality of sensed responses with correspondingelectrode configurations to which the constant stimulus parameters wereapplied to determine an electrode-configuration/response trend andestimating a new electrode configuration that is expected to improve theefficacy according to the electrode-configuration/response trend. 18.The method of claim 15 wherein the selecting procedure comprisesincreasing a stimulus parameter when a stimulus/response trend indicatesthat an increase in the stimulus parameter improves the efficacy of thestimulus.
 19. The method of claim 15 wherein the selecting procedurecomprises decreasing a stimulus parameter when a stimulus/response trendindicates that a decrease in the stimulus parameter improves theefficacy of the stimulus.
 20. The method of claim 15 wherein theapplying, sensing, determining, selecting, repeating and choosingprocedures are repeated on the same patient within a period not greaterthan one week.
 21. The method of claim 15 wherein the applying, sensing,determining, selecting, repeating and choosing procedures are repeatedon the same patient on consecutive days.
 22. The method of claim 15wherein the applying, sensing, determining and selecting procedures arecompleted in a time period not greater than approximately 300 seconds.23. The method of claim 15 wherein two iterations of the applying,sensing, determining and selecting procedures are repeated in a timeperiod not greater than approximately 90 seconds.
 24. The method ofclaim 15 wherein two iterations of the applying, sensing, determiningand selecting procedures are repeated in a time period not greater thanapproximately 180 seconds.
 25. The method of claim 15 wherein twoiterations of the applying, sensing, determining and selectingprocedures are repeated in a time period of approximately 20-90 seconds.